Abnormal immune mechanisms are being studied in patients with HB Ag negative chronic active hepatitis and primary biliary cirrhosis (PBC) selected according to strict diagnostic criteria. T cell mediated help and suppression of pokeweed mitogen-induced immunoglobulin synthesis by B cells has been studied using radio-immunoassays to measure IgG and IgM synthesized by cultures of appropriate mixtures of lymphocyte subpopulations in vitro. The ability of T cells to proliferate when cultured with either autologous or allogeneic irradiated B cells (mixed lymphocyte reactions) or with hapten-modified autologous irradiated b cells has been assessed. Results of these studies include the demonstration in PBC of (i) diminished capacity of T cells to inhibit immunoglobulin synthesis in vitro; (ii) a deficiency of the autologous but not the allogeneic mixed lymphocyte reaction and (iii) a deficiency in the primary but not the secondary proliferative response of T cells to hapten-modified cells. These findings suggest that in PBC there are defects of cell interactions involved in the generation of suppressor effector cells and recognition of exogenous antigens associated with autologous cell surface antigens.